Extended Data Fig. 8: Depletion of LIPIN1 preserves YME1L-mediated proteolysis after inhibition of mTORC1.
From: Lipid signalling drives proteolytic rewiring of mitochondria by YME1L
a, HeLa cells transfected with the indicated esiRNAs were treated with Torin1 for 4 h before immunoblotting. Representative immunoblot and quantification of TIMM17A protein levels are shown (n = 3 independent experiments; fold change (fc) from DMSO control). b, c, Immunoblot analysis of HeLa cells transfected with Gfp or Lipin1 esiRNA (b) or scrambled control (Scr) or Lipin1 siRNA (c) treated with Torin1 for 4 h. Quantification of PRELID1 and TIMM17A protein levels is shown (n = 7 independent experiments (b), n = 6 independent experiments (c)). d, Immunoblot analysis of MEFs transfected with Gfp or Lipin1 esiRNA and treated with Torin1 for 4 h. Quantification of TIMM17A protein levels is shown (n = 5 independent experiments). e, Immunoblot analysis of HeLa cells transfected with the indicated esiRNAs and treated with Torin1 for 4 h (representative data from six independent experiments). f, The mTORC1–LIPIN1–YME1L regulatory axis. Upon inhibition of mTORC1, dephosphorylation of LIPIN1 stimulates its PA-phosphatase activity and leads to a decrease in PA. The depletion of PA inhibits CCTα and therefore limits the supply of PS to mitochondria. Reduced PS transfer to the inner membrane limits accumulation of PE, stimulating YME1L-mediated proteolysis. Mean ± s.e.m.; two-way ANOVA with Tukey’s multiple comparisons test (b–d).
